Fifteen patients (20 to 66 years) with long-standing chronic diarrhea of varying etiology were selected for an open trial of loperamide 2 mg capsules. The optimal daily dose for substantial reduction of the diarrhea ranged from two to seven capsules. Eleven patients showed a significant improvement in stool consistency and stool frequency, and a decrease of abdominal cramps. Loperamide appeared to be ineffective in two patients with cholerrheic diarrhea, and in one patient with laxative-induced diarrhea, and in one patient with diarrhea of unknown etiology. The eleven successfully treated patients then entered a double-blind placebo-controlled trial for ten days or until relapse, the daily dose being identical to the optimal one previously determined in the open phase. The investigator was able to guess the code correctly in ten out of eleven cases. Twenty ileostomy patients (ages 25 to 73 years) volunteered for the evaluation of the inhibitory activity on small intestinal peristalsis by loperamide in a double-blind placebo-controlled cross-over study. Mean daily ileostomy output decreased by 22% in the loperamide period, as compared with the drug-free study phase (P less than 0.001). Of the 20 patients, 16 were able to guess their code correctly, whereas four were uncertain, although their fecal weights were lower with loperamide. Many patients noticed an increased urinary production and experienced an improvement in their ileostomy care during loperamide treatment. Because of its effectiveness, its low side-effect liability and its lack of toxicity, loperamide is considered a promising drug in the symptomatic treatment of chronic diarrhea, and as a reliable agent in the treatment of ileostomy patients.